These studies will provide new insights into the region specific regulatory programs of DCs in mucosal surfaces. We have identified a mucosal plasmacytoid dendritic cell (pDC) subset that has a critical role in limiting intestinal inflammation thereby promoting tissue reconstruction and mucosal restitution. This pDC subset appears as a major DC subset in the intestine during colitis to direct mucosa-specific T cell functions essential for the resolution of inflammation. We hypothesize that mucosal pDCs are principal mediators of mucosal repair responses by controlling the intestine-specific regulatory phenotypes of Foxp3+ Tregs and Th17 cells. We will define key mechanisms that allow regulatory mucosal pDCs to effectively suppress inflammatory signals and to mediate mucosal protection. Defining the functional role of this newly discovered pDC subset in the regulation of mucosal inflammation will provide pivotal insights into the mechanisms that mediate mucosa specific control of regulatory T cells required for tissue repair in the highly antigenic environment of the intestine.